Evidence is mounting that hormone replacement therapy (HRT) is harmful in women with existing coronary artery disease. Studies also indicate that high dosages of antioxidant vitamins may worsen cardiovascular outcomes. A randomized, placebo-controlled study by Waters and associates added information about the use of HRT and antioxidant vitamins through analysis of angiographic measurements and clinical end points such as cardiovascular death, nonfatal myocardial infarction, and stroke (alone and in combination). Other end points included coronary artery surgery, pulmonary embolus, and cancer.

In the Women’s Angiographic Vitamin and Estrogen (WAVE) trial, 423 postmenopausal women with existing coronary stenosis were randomized into the following four treatment groups: HRT and vitamins E and C; HRT placebo and vitamins E and C; vitamin placebos and HRT; and vitamin placebos and HRT placebo. Dosages were as follows: vitamin E, 400 IU twice daily; vitamin C, 500 mg twice daily; conjugated equine estrogens, 0.625 mg per day in women with previous hysterectomy; and conjugated equine estrogen/ medroxyprogesterone acetate, 0.625 mg/2.5 mg per day in women who had not had a hysterectomy. Of the 423 participants who received baseline angiography, 306 had exit angiography, with a mean interval of 2.8 years between angiograms.

Coronary angiography showed a greater decrease in mean lumen diameter in the three treatment groups than in the all-placebo group, although no decrease was statistically significant. Analysis of clinical events showed that overall mortality was lowest in the all-placebo group and highest in the group receiving both vitamins and HRT. More women who received HRT died or had a non-fatal myocardial infarction (a composite category) than women who took placebo, although the difference was not statistically significant. All-cause mortality increased significantly in the women who took antioxidant vitamins compared with those who took placebo; a trend suggested an increase in cardiovascular deaths in the vitamin-treated group.

Overall, the WAVE trial supports previous trials that showed no cardiovascular benefits for the use of HRT or antioxidant vitamins in patients with coronary artery disease. On the contrary, these interventions may be harmful, at least in the short term. The authors recommend against giving HRT or high doses of vitamin E or C to postmenopausal women who have coronary disease.